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Oral Antibiotic for Bacterial Pneumonia Meets Main Objective in Late-Stage Trial
Positive results have been reported from a pivotal phase III study of solithromycin oral capsules (Cempra Pharmaceuticals) in the treatment of patients with community-acquired bacterial pneumonia (CABP).
In the intent-to-treat population (ITT, all randomized patients), solithromycin met the trial’s primary objective of statistical non-inferiority of the early clinical response at 72 hours after the initiation of therapy compared with moxifloxacin (Avelox, Merck; generics).
Solithromycin also met a key secondary objective of non-inferiority in clinical success at the short-term follow-up visit (5 to10 days after the end of therapy) in both the ITT and clinically evaluable populations.
The point estimates for the primary endpoint of early clinical response were 78.2% for solithromycin and 77.9% for moxifloxacin. The results were similar in the combined total patient population; however, initial subgroup analyses by age indicated that the difference in point estimates became larger with increasing age and favored solithromycin in the ITT early clinical response groups.
The Solitaire-Oral trial was a double-blind, active-controlled, global study involving 860 adult patients with moderate to moderately severe CABP. The patients were randomly assigned to receive either oral solithromycin as an 800-mg loading dose followed by 400 mg once daily for a total of 5 days, or oral moxifloxacin dosed at 400 mg once daily for 7 days. The study’s primary objective was non-inferiority of the early clinical response at 72 hours, defined as having improvement in at least two of the following four symptoms (without worsening of any) in the ITT population: cough, shortness of breath, chest pain, and sputum production. The study was designed to provide 90% power to demonstrate non-inferiority in the early clinical response rate for solithromycin versus moxifloxacin.
Secondary endpoints included the clinical success rate at the short-term follow-up visit 5 to 10 days after the last dose of study drug in the ITT and clinically evaluable populations, and a comparison of the safety and tolerability of solithromycin and moxifloxacin.
Serious adverse events (SAEs) occurred with equal frequency in both treatment arms (less than 7% of patients), and no SAEs were considered related to a study drug. The most common AEs associated with solithromycin compared with moxifloxacin included headache (4.5% vs. 2.5%, respectively), diarrhea (4.2% vs. 6.5%), nausea (3.5%, vs. 3.9%), emesis (2.4% vs. 2.3%), and dizziness (2.1% vs. 1.6%).
CABP is the number one cause of death from an infection, particularly in the very young and the elderly. It is one of the most commonly diagnosed bacterial infections in the U.S., resulting in 5 to 10 million cases per year. Although many strains of Streptococcus pneumoniae (the primary CABP pathogen) are resistant to currently approved macrolides, this class of antibiotics remains among the most commonly prescribed antibacterial drugs for CABP, both in the hospital and in community settings.
Solithromycin is a next-generation macrolide, the first fluoroketolide, and has activity against most macrolide-resistant strains. In vitro and in vivo studies have shown activity against S. pneumoniae as well as an extended spectrum of activity against community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA), streptococci, Haemophilus, enterococci, Mycobacterium avium, and animal models of malaria. It is also active against atypical bacteria, such as legionella, chlamydia, mycoplasma and ureaplasma, and against gonococci and other organisms that cause genitourinary-tract infections.
Solithromycin is eight to 16 times more potent than azithromycin (Zithromax, Pfizer; generics) and is active against azithromycin-resistant strains. The activity of solithromycin against resistant strains is based on its ability to interact with three sites on the bacterial ribosome, compared with one site for current macrolides. This binding to three ribosomal sites is expected to limit the development of resistance.
Source: Cempra Pharmaceuticals; January 4, 2015.